MXenes, a rapidly expanding family of two-dimensional transition metal carbides, nitrides, and carbonitrides, are versatile nanomaterials with broad applications in energy, catalysis, sensing, and biomedicine. While most studies have focused on mono–transition-metal MXenes (e.g., Ti 3 C2 Tx), recent advances have enabled the synthesis of double-transition-metal (DTM) MXenes, in which two distinct transition metals occupy ordered or disordered atomic arrangements. This added compositional and structural complexity broadens property range, enabling enhanced oxidative stability, programmable degradation behavior, tunable electromagnetic responses, and improved near-infrared optical absorption. These attributes position DTM MXenes as a compelling biomedical materials platform. In this review, we summarize the discovery, synthesis strategies, and physicochemical characteristics of DTM MXenes, with systematic comparisons to classical mono–transition-metal MXenes to elucidate multi-metal structure–property relationships. We then critically examine emerging biomedical applications of DTM MXenes, including photothermal cancer therapy, multimodal imaging, drug delivery, antibacterial activity, and tissue engineering, highlighting insights from both in vitro and in vivo studies. Key challenges for clinical translation, including scalable synthesis, compositional and structural control, long-term biocompatibility, biodegradation, and regulatory considerations, are discussed. By integrating perspectives from materials science, nanotechnology, and biomedical engineering, this review outlines opportunities, limitations, and future directions toward safe, effective multifunctional DTM MXene nanomedicine platforms.